Cholesterol and 7-dehydrocholesterol are end products of epidermal sterol metabolism. Cholesterol can be related to normal keratinization and the development of epidermal barrier function. Seven-dehydrocholesterol is the direct precursor of vitamin D3 which is produced by a photoreaction in the epidermis. Defective epidermal barrier function and mild 25-OHD3 deficiency associated with osteoporosis have been demonstrated with aging. The hypothesis that the senescent epidermis is quantitatively or qualitative defective in the production of sterols will be tested. This defect could result in dry, scaly, itchy skin (xerosis) and inadequate vitamin D production. Cholesterol and 7-dehydrocholesterol will be measured in aging human epidermis by using high pressure liquid chromatography, TLC, and gas liquid chromatography. The regulation of epidermal sterol metabolism in aging will be compared with young normal epidermis by determining the rate of synthesis of cholesterol and other sterols from 14C-mevalonate. Appendage freed epidermis will be used in vitro studies. Patients with clinically evident xerosis and with mild vitamin D deficiency associated with osteoporosis will also be studied in an effort to clarify the pathophysiology of these disorders. Data generated in this work will interface broadly with the study of disorders of keratinization and will add to knowledge of the endogenous production of vitamin D.